Overview

Also Known As:Bax^-

Homozygous Bax^tm1Sjk mice display aberrant apoptosis with hyperplasia displayed in various tissues, including thymocytes, B cells, and cells of the reproductive organs.

Donating Investigator

Dr. Stanley J. Korsmeyer, Dana-Farber Cancer Institute

Genetic overview

Genetic Background	Generation

Bax^tm1Sjk

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Bax	BCL2-associated X protein

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Research Applications

Developmental Biology Research
Apoptosis Research
Cancer Research
Immunology, Inflammation and Autoimmunity Research
Reproductive Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Bax^tm1Sjk mutation are viable but display lineage-specific aberrations in cell death. Thymocytes and B cells from homozygous mutant mice display hyperplasia. Ovaries contain unusual atretic follicles with excess granulosa cells while Bax-deficient males are infertile. There is an accumulation of atypical premeiotic germ cells and no mature haploid sperm found in seminiferous tubules. Multinucleated giant cells and dysplastic cells accompany massive cell death.

Used in conjunction with strain B6.129-Bak1^tm1Thsn/J (see Stock No. 004183), to generate the double knock-out Bak/Bax, a model for demonstrating severe defects in the regulation of apoptosis during development and tissue homeostasis.

Coat color of Bax^tm1Sjk mice
The coat color loci tyrosinase (Tyr) and pink-eyed dilution (p) are linked to the Bcl2-associated X protein (Bax) gene. According to backcross data from the Mouse Genome Database, Bax is at 23.00 cM, p is at 28.00 cM, and Tyr is at 44.00 cM on chromosome 7. The targeted disruption of the Bax gene was performed in a 129-derived RW-4 ES cell line (A^w/A^w p Tyr^c-ch/p Tyr^c) and was backcrossed 8 generations to C57BL/6 (a/a +^p +^Tyr-c/+^p +^Tyr-c; nonagouti black) before arriving at The Jackson Laboratory. The Jackson Laboratory's live colony of B6.129X1-Bax^tm1Sjk/J mice (June 2019) is no longer segregating at the Tyr locus and do not retain the p allele from the 129 ES cell line: coat and eye color is black. However, the mice that were the source of the cryopreserved sperm (cryopreserved in 2003 at N12) may have been segregating at the Tyr locus and might retain the p allele from the 129 ES cell line. Thus, matings of Bax heterozygous (+/-) mice recovered from the cryorepository stock (N12 cryopreserved sperm) may produce progeny of varying coat color including black, white, chinchilla, light chinchilla, or grey, with all but the black mice having pink eyes. Because the potential for crossover between the p and Bax loci is small (roughly 5%), progeny from cryorecovered stock that are grey in color and have pink eyes most likely are homozygous for the targeted Bax gene (-/-).

Development

A Bax targeting vector substituted PGK-Neo for exons 2 through 5, deleting BH1 and BH2 and the capacity for a functional protein. This construct was was electroporated into 129-derived RW-4 ES cell line (A^w/A^w p Tyr^c-ch/p Tyr^c). The resulting chimeric animals were tested for germline transmission. The mice were then backcrossed 8 generations to C57BL/6 (a/a +^p +^Tyr-c/+^p +^Tyr-c; nonagouti black) before arriving at The Jackson Laboratory. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Knudson CM; Tung KS; Tourtellotte WG; Brown GA; Korsmeyer SJ. 1995. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270(5233):96-9PubMed: 7569956 MGI: J:29253

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Genetics

Bax^tm1Sjk

Allele Symbol: Bax^tm1Sjk

Allele Name	targeted mutation 1, Stanley J Korsmeyer
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Bax^-; Bax1
Gene Symbol and Name	Bax, BCL2-associated X protein
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	7
Molecular Note	A neomycin selection cassette replaced exons 2 through 4 and part of exon 5, which encode sequences that correspond to the two BCL2 homology domains BH1 and BH2. Immunoblots did not detect the endcoded protein in tissue lysates derived from homozygous mice.
Mutations Made By	Dr. Stanley Korsmeyer, Dana-Farber Cancer Institute

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Bax^tm1Sjk related

Developmental Biology Research
- Internal/Organ Defects
  - gonads
Apoptosis Research
- Endogenous Regulators
Cancer Research
- Genes Regulating Growth and Proliferation
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
Reproductive Biology Research
- Developmental Defects Affecting Gonads
- Fertility Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Bak1^tm1Thsn/Bak1^tm1Thsn Bax^tm1Sjk/Bax^tm1Sjk
involves: 129S1/Sv * 129S1/SvImJ * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

circling
- display circling behavior when exposed to external stress

seizures
- stress-induced seizure activity

homeostasis/metabolism phenotype

decreased physiological sensitivity to xenobiotic
- thymocytes are resistant to treatment with etoposide, a chemotherapeutic agent that normally induces cell death

immune system phenotype

abnormal B cell morphology
- B220+ B cells present in the lymph node and spleen are skewed toward a B220^brightIgD- phenotype, indicating an increase in the number of class-switched or memory B cells

abnormal splenocyte physiology
- isolated splenocytes cultured in suspension show enhanced survival

abnormal T cell morphology
- T cells that accumulate in mutants are skewed toward a memory cell phenotype

enlarged lymph nodes

enlarged spleen

increased leukocyte cell number

increased lymphocyte cell number
- increases within the circulation and the peripheral lymphoid organs
- lymphocytic infiltration is seen in parenchymal organs, liver, and kidney

increased spleen red pulp amount
- expanded red pulp contains a large increase in the number of plasma cells and histiocytes

increased spleen white pulp amount
- pronounced hyperplasia

limbs/digits/tail phenotype

interdigital webbing
- mutants retain interdigital webs on both fore and rear paws

cellular phenotype

decreased cellular sensitivity to gamma-irradiation
- thymocytes show enhanced survival compared to wild-type when exposed to gamma irradiation

mortality/aging

neonatal lethality, incomplete penetrance
- majority die within 48 hours of birth, although some survive to adulthood

nervous system phenotype

abnormal brain morphology
- increase in the number of neurons in multiple regions of the brain
- large accumulation of small neuronal cells (neural stem cells) with dense chromatin staining in the periventricular region

increased brain size

increased neuron number
- in multiple regions of the brain

seizures
- stress-induced seizure activity

reproductive system phenotype

vagina atresia
- seen in all adult females

growth/size/body region phenotype

enlarged spleen

hearing/vestibular/ear phenotype

abnormal hearing physiology
- unresponsive to auditory stimuli

hematopoietic system phenotype

abnormal B cell morphology
- B220+ B cells present in the lymph node and spleen are skewed toward a B220^brightIgD- phenotype, indicating an increase in the number of class-switched or memory B cells

abnormal definitive hematopoiesis
- hematopoietic colony assays show an increase in the number of myeloid colony forming units and a mild increase in erythroid and megakaryocyte colony forming units

abnormal splenocyte physiology
- isolated splenocytes cultured in suspension show enhanced survival

abnormal T cell morphology
- T cells that accumulate in mutants are skewed toward a memory cell phenotype

anemia
- mild anemia

enlarged spleen

increased leukocyte cell number

increased lymphocyte cell number
- increases within the circulation and the peripheral lymphoid organs
- lymphocytic infiltration is seen in parenchymal organs, liver, and kidney

increased spleen red pulp amount
- expanded red pulp contains a large increase in the number of plasma cells and histiocytes

increased spleen white pulp amount
- pronounced hyperplasia

thrombocytopenia

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
involves: 129X1/SvJ

cellular phenotype

abnormal male germ cell apoptosis
- increased male germ cell apoptosis

azoospermia
- absence of sperm in the epididymis and vas deferens

decreased neuron apoptosis
- developmental sympathetic and motor neuronal death is reduced

immune system phenotype

enlarged spleen

increased B cell number

increased thymocyte number
- 1.6 fold increase in thymocyte number relative to wild-type
- normal distribution of maturational subsets (CD4-CD8-, CD4+CD8+, CD4+, CD8+ cells)

mammalian phenotype

nervous system phenotype
- Normal - mice exhibit normal mammary gland innervation

nervous system phenotype

abnormal facial motor nucleus morphology
- mutants exhibit a large reduction in motor neuron death in the facial nucleus following neonatal axotomy compared to wild-type

abnormal phrenic nerve morphology
- the phrenic nerve is thicker in mutants, however neuromuscular synapses were normal

abnormal proprioceptive neuron morphology
- about 30% of pSNs in the rostral lumbar DRG have cell body diameters in the wild-type range, with 70% having smaller somatic diameters

abnormal superior cervical ganglion morphology
- superior cervical ganglion of neonates contains 2.5 and 1.8 times more neurons than wild-type and heterozygous ganglia, respectively

abnormal sympathetic neuron morphology
- sympathetic neurons from superior cervical ganglion show a dramatic reduction of death after trophic factor (NGF) deprivation

decreased neuron apoptosis
- developmental sympathetic and motor neuronal death is reduced

increased motor neuron number
- contralateral nonaxotomized facial nucleus shows a 51% increase in neuronal number relative to wild-type at 4 weeks of age
- mutants display an increase in the number of small- to medium-sized motor neurons

increased sensory neuron number
- number of proprioceptive sensory neurons (pSNs) is increased by 2-fold compared to wild-type controls

reproductive system phenotype

abnormal male germ cell apoptosis
- increased male germ cell apoptosis

abnormal ovarian follicle morphology
- atretic follicles with excess granulosa cells

abnormal seminiferous tubule morphology
- disordered

arrest of spermatogenesis
- accumulation of premeiotic germ cells

azoospermia
- absence of sperm in the epididymis and vas deferens

male infertility

endocrine/exocrine gland phenotype

abnormal ovarian follicle morphology
- atretic follicles with excess granulosa cells

abnormal seminiferous tubule morphology
- disordered

increased thymocyte number
- 1.6 fold increase in thymocyte number relative to wild-type
- normal distribution of maturational subsets (CD4-CD8-, CD4+CD8+, CD4+, CD8+ cells)

growth/size/body region phenotype

enlarged spleen

hematopoietic system phenotype

enlarged spleen

increased B cell number

increased thymocyte number
- 1.6 fold increase in thymocyte number relative to wild-type
- normal distribution of maturational subsets (CD4-CD8-, CD4+CD8+, CD4+, CD8+ cells)

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6

cellular phenotype

abnormal axon extension
- neurite outgrowth is significantly less than that of Isl1^tm1(cre)Cos Mapt^{tm1(Ewsr1/Etv4)Arbr} heterozygotes with or without treatment with neurotrphin-3

nervous system phenotype

abnormal axon extension
- neurite outgrowth is significantly less than that of Isl1^tm1(cre)Cos Mapt^{tm1(Ewsr1/Etv4)Arbr} heterozygotes with or without treatment with neurotrphin-3

abnormal dorsal root ganglion morphology
- dorsal root ganglia neurons survive without neurotrophic factors

increased sensory neuron number
- apoptosis rates are decreased resulting in increased number of neurons in the lumbar dorsal root ganglia (170% of wild-type numbers)

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
involves: 129X1/SvJ * C57BL/6

endocrine/exocrine gland phenotype

abnormal ovarian folliculogenesis
- follicles persisted in aged females (20 to 22 months old)
- increased number of follicles observed at 42 days
- reduced incidence of atresia of primordial and primary follicles relative to wild-type

increased mature ovarian follicle number
- increased number of follicles observed at 42 days of age
- persistence of hundreds of follicles of all developmental stages in aged females (20 to 22 months old)

nervous system phenotype

abnormal dorsal root ganglion morphology
- the number of dorsal root ganglia neurons in L4 is increased relative to in wild-type mice

reproductive system phenotype

abnormal ovarian folliculogenesis
- follicles persisted in aged females (20 to 22 months old)
- increased number of follicles observed at 42 days
- reduced incidence of atresia of primordial and primary follicles relative to wild-type

increased mature ovarian follicle number
- increased number of follicles observed at 42 days of age
- persistence of hundreds of follicles of all developmental stages in aged females (20 to 22 months old)

uterus hypertrophy
- ovarian steroid-driven uternine hypertrophy is observed in aged females (20 to 22 months old)

Genotype: Bax^tm1Sjk/Bax⁺
involves: 129X1/SvJ

nervous system phenotype

abnormal sympathetic neuron morphology
- cultures of sympathetic neurons grown in the presence of NGF before being deprived of NGF, die with slower kinetics than wild-type, such that after 8 days, 14% of neurons remain viable compared to none in controls

increased motor neuron number
- modest 13% increase in the total number of facial motor neurons at 4 weeks of age relative to wild-type

The following phenotype relates to a compound genotype created using this strain

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
B6.129X1-Bax/J

cellular phenotype

azoospermia

endocrine/exocrine gland phenotype

abnormal seminiferous tubule morphology
- some tubules have an accumulation of early germ cells while others have fewer germ cells than normal
- the spermatogonia layer is thicker than in wild-type being up to 3 cell layers thick

decreased testis weight
- in adults testes weigh about 60% that of wild-type

growth/size/body region phenotype

decreased body weight
- seen in about 50% of mice

mammalian phenotype

nervous system phenotype
- cultured enteric neurons from Bax-deficient embryos that are GDNF-deprived show no significant differences in survival relative to enteric neurons from conditionally-inactivated Gfra1-null mice

reproductive system phenotype

abnormal seminiferous tubule morphology
- some tubules have an accumulation of early germ cells while others have fewer germ cells than normal
- the spermatogonia layer is thicker than in wild-type being up to 3 cell layers thick

abnormal spermatogenesis
- at P15 the number of germ cells in the testis is increased and these are mostly c-Kit+ early germ cells, but in adult males the number of germ cells is decreased by up to 10-fold compared to wild-type

arrest of male meiosis
- arrests before the completion of meiosis in the preleptotene spermatocyte stage

azoospermia

decreased testis weight
- in adults testes weigh about 60% that of wild-type

male infertility
- males but not females are sterile

References

Knudson CM; Tung KS; Tourtellotte WG; Brown GA; Korsmeyer SJ. 1995. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270(5233):96-9PubMed: 7569956 MGI: J:29253

Additional References

Forger NG; Rosen GJ; Waters EM; Jacob D; Simerly RB; de Vries GJ. 2004. Deletion of Bax eliminates sex differences in the mouse forebrain. Proc Natl Acad Sci U S A 101(37):13666-71PubMed: 15342910 MGI: J:92614
Khaled AR; Li WQ; Huang J; Fry TJ; Khaled AS; Mackall CL; Muegge K; Young HA; Durum SK. 2002. Bax deficiency partially corrects interleukin-7 receptor alpha deficiency. Immunity 17(5):561-73PubMed: 12433363 MGI: J:93139
Knudson CM; Korsmeyer SJ. 1997. Bcl-2 and Bax function independently to regulate cell death. Nat Genet 16(4):358-63PubMed: 9241272 MGI: J:42051
Lu YP; Lou YR; Peng QY; Xie JG; Conney AH. 2004. Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in the epidermis of p53 and Bax knockout mice. Cancer Res 64(14):5020-7PubMed: 15256477 MGI: J:91506
Nicholls PK; Schorle H; Naqvi S; Hu YC; Fan Y; Carmell MA; Dobrinski I; Watson AL; Carlson DF; Fahrenkrug SC; Page DC. 2019. Mammalian germ cells are determined after PGC colonization of the nascent gonad. Proc Natl Acad Sci U S A 116(51):25677-25687PubMed: 31754036 MGI: J:282807
Yin C; Knudson CM; Korsmeyer SJ; Van Dyke T. 1997. Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 385(6617):637-40PubMed: 9024662 MGI: J:38331

Additional - Bax^tm1Sjk related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Bax Alternate1
- Standard PCR:Bax
- Standard PCR:Bax
- Genotyping resources and troubleshooting
Breeding Considerations

The strain is maintained through heterozygous matings. BAX-deficient males are infertile and females are extremely poor breeders. A slightly lower than Mendelian ratio may be seen in matings of heterozygous animals.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the Bax^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002994 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Bax<tm1Sjk>

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:Bax-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Baxtm1Sjk

Allele Symbol: Baxtm1Sjk

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Baxtm1Sjk related

Mammalian Phenotype Terms by Genotype

Genotype: Bak1tm1Thsn/Bak1tm1Thsn Baxtm1Sjk/Baxtm1Sjkinvolves: 129S1/Sv * 129S1/SvImJ * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

homeostasis/metabolism phenotype

immune system phenotype

limbs/digits/tail phenotype

cellular phenotype

mortality/aging

nervous system phenotype

reproductive system phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

Genotype: Baxtm1Sjk/Baxtm1Sjkinvolves: 129X1/SvJ

cellular phenotype

immune system phenotype

mammalian phenotype

nervous system phenotype

reproductive system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Baxtm1Sjk/Baxtm1Sjkinvolves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6

cellular phenotype

nervous system phenotype

Genotype: Baxtm1Sjk/Baxtm1Sjkinvolves: 129X1/SvJ * C57BL/6

endocrine/exocrine gland phenotype

nervous system phenotype

reproductive system phenotype

Genotype: Baxtm1Sjk/Bax+involves: 129X1/SvJ

nervous system phenotype

Genotype: Baxtm1Sjk/Baxtm1SjkB6.129X1-Bax/J

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

mammalian phenotype

reproductive system phenotype

References

Additional References

Additional - Baxtm1Sjk related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:Bax^-

Bax^tm1Sjk

Allele Symbol: Bax^tm1Sjk

Genotype: Bax^tm1Sjk related

Genotype: Bak1^tm1Thsn/Bak1^tm1Thsn Bax^tm1Sjk/Bax^tm1Sjk
involves: 129S1/Sv * 129S1/SvImJ * 129X1/SvJ * C57BL/6

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
involves: 129X1/SvJ

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
involves: 129X1/SvJ * C57BL/6

Genotype: Bax^tm1Sjk/Bax⁺
involves: 129X1/SvJ

Genotype: Bax^tm1Sjk/Bax^tm1Sjk
B6.129X1-Bax/J

Additional - Bax^tm1Sjk related